| Title : (2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]tr iazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes - Edmondson_2006_J.Med.Chem_49_3614 |
| Author(s) : Edmondson SD , Mastracchio A , Mathvink RJ , He J , Harper B , Park YJ , Beconi M , Di Salvo J , Eiermann GJ , He H , Leiting B , Leone JF , Levorse DA , Lyons K , Patel RA , Patel SB , Petrov A , Scapin G , Shang J , Roy RS , Smith A , Wu JK , Xu S , Zhu B , Thornberry NA , Weber AE |
| Ref : Journal of Medicinal Chemistry , 49 :3614 , 2006 |
|
Abstract :
A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]tr iazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes. |
| PubMedSearch : Edmondson_2006_J.Med.Chem_49_3614 |
| PubMedID: 16759103 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | MK0626 |
| Gene_locus | human-DPP4 |
| Structure | 2FJP |
Edmondson SD, Mastracchio A, Mathvink RJ, He J, Harper B, Park YJ, Beconi M, Di Salvo J, Eiermann GJ, He H, Leiting B, Leone JF, Levorse DA, Lyons K, Patel RA, Patel SB, Petrov A, Scapin G, Shang J, Roy RS, Smith A, Wu JK, Xu S, Zhu B, Thornberry NA, Weber AE (2006)
(2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]tr iazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Journal of Medicinal Chemistry
49 :3614
Edmondson SD, Mastracchio A, Mathvink RJ, He J, Harper B, Park YJ, Beconi M, Di Salvo J, Eiermann GJ, He H, Leiting B, Leone JF, Levorse DA, Lyons K, Patel RA, Patel SB, Petrov A, Scapin G, Shang J, Roy RS, Smith A, Wu JK, Xu S, Zhu B, Thornberry NA, Weber AE (2006)
Journal of Medicinal Chemistry
49 :3614